PROJECT SUMMARY This proposal is a competitive renewal application for five years of support to continue the 40-year-old Yale Postdoctoral Training Program in Investigative Hepatology. The goal of this training program is to provide basic laboratory, translational, or clinical research training for physicians who have completed clinical training in gastroenterology in preparation for careers as independent investigators in academic hepatology and to provide research training for recent PhD graduates to prepare them for careers as independent investigators in basic liver-related research. The program draws on the exceptional liver research environment at Yale, including a large pool of preceptors who are internationally recognized investigators that are well funded and have extensive mentorship experience. The program's trainees in turn have a long track record of going on to become leaders in the field of hepatology; in recent years the majority of trainees have obtained independent funding, and nearly all have published multiple papers related to their training and have gone on to academic or other research-intensive careers. The program will continue to train four postdoctoral fellows at a time, and individual trainees will be supported for two to three years. Selection of trainees will be based on strong prior research experience and commitment to liver-related research. This training program will use the combined resources of the NIDDK-funded Yale Liver Center, the Yale Digestive Diseases Section, and facilities of the participating faculty including the Departments of Internal Medicine, Cell Biology, Cellular and Molecular Physiology, Human Genetics, Microbial Pathogenesis, Pediatrics, and Pharmacology. The major research areas represented include (1) liver infection, inflammation, and immunobiology, (2) hepatic metabolism and steatosis, (3) bile secretion and cholestasis, (4) liver cancer, (5) fibrosis and cirrhosis and (6) basic liver biology and pathobiology. The Section of Digestive Diseases, the Medical School's Investigative Medicine Program as well as enrichment programs provided by the Liver Center together provide a strong and liver-oriented educational curriculum. Trainees are encouraged to audit or enroll in specific courses in the School of Medicine or the School of Public Health, attend annual laboratory and lecture courses designed for physician trainees in the Department of Medicine, and are required to attend both Hepatology and Basic Science Journal Clubs, plus weekly research and pathophysiology seminars. Progress is monitored through several mechanisms including Research in Progress seminars and individual Progress Committees.